Meso ring-opening

Although the enantioselective intermolecular addition of aliphatic alcohols to meso-epoxides with (salen)metal systems has not been reported, intramolecular asymmetric ring-opening of meso-epoxy alcohols has been demonstrated. By use of monomeric cobalt acetate catalyst 8, several complex cyclic and bicydic products can be accessed in highly enantioenriched form from the readily available meso-epoxy alcohols (Scheme 7.17) [32]. 

The first example of asymmetric catalytic ring-opening of epoxides with sp2-hybridized carbon-centered nucleophiles was reported by Oguni, who demonstrated that phenyllithium and a chiral Schiff base ligand undergo reaction to form a stable system that can be used to catalyze the enantioselective addition of phenyllithium to meso-epoxides (Scheme 7.24) [48]. Oguni proposed that phenyllithium... 

Enantioselective alcoholysis of racemic, prochiral, or meso cyclic anhydrides can be catalyzed by hydrolases, yielding the corresponding monoesters (Eigure 6.25). In most cases, the enantioselectivity was moderate ]75-77]. Organometallic catalysts or organocatalysts such as cinchona alkaloids are often more efficient than enzymes for the stereoselective ring opening of cyclic anhydrides. 

An early example of the use of a subcatalytic amoimt of sparteine for the activation of an organolithium nucleophile was reported by Lautens et al. in the carbometallation of a meso-unsaturated oxabicycle 25, with ring opening leading to the substituted cycloheptene derivative 26 (Scheme 4) [4]. Both yield and enantiomeric excess remained virtually unchanged when the ratio n-BuLi sparteine was lowered to 1 0.15. However, when a 3 mol% amount of the ligand 1 was used, a 20% decrease in enantioselectivity was observed. 

The analogous chromium complex was used in the asymmetric ring opening of meso epoxides with trimethylsilyl azide [15] (Scheme 4). In this case a strong dependence on the anion of the ionic hquid was observed. Anions leading to hydrophobic ionic hquids, such as PFe" and SbFe", led to high... 

Method B was also used in the preparation of occluded (salen)Cr complexes. ligands Ih and li were prepared within the pores of Cr -exchanged EMT and Y zeolites, respectively [25]. These complexes were tested as catalysts in the ring opening of meso-epoxides with trimethylsilyl azide (Scheme 4). The occluded complexes showed a dramatic decrease in catalytic... 

Among recently described new Pd-catalysed enantioselective reactions, the ring opening of meso oxabicyclic alkenes with dialkyl zinc reagents in the presence of chiral P/P and P/N ligands reported by Tautens el al. constitutes a synthetically outstanding C-C bond-forming desymmetrization reaction. 

Scheme 10.72 Ring openings of meso heterobicyclic alkenes with Fesulphos ligands.

Heck-type reactions 233-41 Heck reaction 233-5 Henry reactions 318-20, 321, 322 meso heterobicyclic alkenes, ring opening of 348-50 heterodonating ligands 9 heterodonor ligands with... 

Lactide (LA), the cyclic diester of lactic acid, has two stereogenic centers and hence exists as three stereoisomers L-lactide (S,S), D-lactide (R,R), and meso-lactide (R,S). In addition, rac-lactide, a commercially available racemic mixture of the (R,R) and (S,S) forms, is also frequently studied. PLA may exhibit several stereoregular architectures (in addition to the non-stereoregular atactic form), namely isotactic, syndiotactic, and heterotactic (Scheme 15). The purely isotactic form may be readily prepared from the ROP of L-LA (or D-LA), assuming that epimerization does not occur during ring opening. The physical properties, and hence medical uses, of the different stereoisomers of PLA and their copolymers vary widely and the reader is directed to several recent reviews for more information.736 740-743... 

The enantiomorphic site selectivity of (R)-(—)-(263) allows highly syndiotactic PLA to be prepared via the polymerization of meso-LA (Mn = 12,030, Mn calc= 13,540, Mw/Mn= 1.05).802 The ring opening of meso-LA by (R)-(—)-(263) occurs to produce a syndiotactic propagating chain bound to the metal via an (S)-lactic acid unit.803 Attempts to produce syndiotactic PLA via the ROP of meso-LA using rac-( )-(263) instead afforded heterotactic-biased material. 

Complexes of other metals such as gallium, indium, lead, and antimony have also been used as Lewis acids. Catalytic enantioselective meso-epoxide ring-opening reactions using a chiral gallium(III) catalyst (Ga-Li-linked-BINOL) have been reported (Scheme 84).348 The chemical yields are much improved by linking two BINOL units. 

Using the catalytic system described above, the enantioselective opening of meso epoxides could also be pursued. Although many excellent examples of ring-opening of meso epoxides by Sn2 reactions have recently been reported, the reaction planned here is conceptually different [40]. In the SN2 reaction, the path of the incoming nucleophile has to be controlled. In the titanocene-catalyzed reaction, the intermediate radical has to be formed selectively. If an intermediate similar to that invoked in the Bartmann ring-open-... 

Stereoselective ring cleavage and monoesterification of chiral Meldrum s acid derivatives has been achieved in high yield with a 34% enantiomeric excess under phase-transfer catalytic conditions in the presence of A-benzylquininium chloride [29]. A similar asymmetric ring-opening of prochiral (meso) acid anhydrides with... 

Ring-opening by azide and the subsequent work-up is not ideal from a point of view of safety and costs and ring-opening by other nucleophiles is attractive. Furthermore, the use of meso compounds restricts the use of the catalyst to a small number of substrates and useful products. 

To avoid the inherent limitations of a kinetic resolution process, the reaction was extended to desymmetrization of prochiral meso epoxides. A number of cyclic di-methylidene epoxides were synthesized and subjected to treatment with Et2Zn in the presence of Cu(OTf)2 and ligands 42 or 43. As in the case mentioned above, ligand 42 was superior in terms of selectivity. Cydohexane derivative 46 gave the ring-opened product with a 97% ee and in a 90% isolated yield, with a y/a ratio of 98 2 (Scheme 8.28). The other substrates investigated produced sigmficantly lower ees of between 66% and 85%. 

Table 11. Asymmetric catalytic ring opening of meso stilbene oxide with aniline using...

The same catalyst 73 also worked efficiently for catalytic asymmetric ring opening of cyelohexene oxide and meso-stilbene oxide [34] with anilines under mierowave irradiation to afford P-amino alcohols in high yield (up to 95%) and good enantioseleetivities (ee up to 55%). The reaction under mierowave was found to be 10 times faster than traditional oil-bath heating without compromising enantioselectivity. Also the ee for the produet P-amino aleohols was comparable with the values obtained at room temperature (Table 12). 

Eppley, A. W. Totah, N. I. (1997) A new chiral titanium species for the ring opening reactions of meso-epoxides., Tetrahedron, 53 16545-16552. 

Schaus, S. E. Larrow, J. F. Jacobsen, E. N. (1997) Practical synthesis of enantiopure cyclic 1,2-amino alcohols via catalytic asymmetric ring opening of meso-epoxides., J. 

Nugent, W. A. (1998) Desymmetrization of meso-epoxides with halides A new catalytic reaction based on mechanistic insight, J. Am. Chem. Soc., 120 7139-7140. Bruns, S. Haufe, G. (1999) Catalytic asymmetric ring opening of epoxides to chlorohydrins with mild chloride donors and enantiopure titanium complexes.. 

Reymond, S. Brunei, J. M. Buono, G. (2000) New development in the enantioselective ring opening of meso-epoxides by various ion silicon sources catalyzed by an o-methoxyaryldiazaphosphonamide Lewis base., Tetrahedron Asymmetry, 11 4441-4445. 

Nakajima, M. Saito, M. Uemura, M. Hashimoto, S. (2002) Enantioselective ring opening of meso-epoxides with tetrachlorosilane catalyzed by chiral bipyridine N,N -dioxide derivatives.. Tetrahedron Lett., 43 8827-8829. 

Tokuoka, E. Kotani, S. Matsimaga, H. Ishizuka, T. Hashimoto, S. Nakajima, M. (2005) Asymmetric ring opening of meso-epoxides catalyzed by the chiral phosphine oxide BINAPO., Tetrahedron Asymmetry 16 2391-2392. 

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